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Article

SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues

1
Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
2
Department of Biochemistry, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University, Jerusalem 9112102, Israel
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Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem 9112102, Israel
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Department of Cardiothoracic Surgery, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
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Department of Otorhinolaryngology, Sheba Medical Center, Ramat Gan 52621, Israel
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Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
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Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University, Jerusalem 9112102, Israel
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Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat Gan 52621, Israel
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School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel
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The Center for Integrative Complementary Medicine, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
*
Author to whom correspondence should be addressed.
Academic Editors: Elmostafa Bahraoui and Remi Planes
Viruses 2022, 14(7), 1583; https://doi.org/10.3390/v14071583
Received: 28 June 2022 / Revised: 19 July 2022 / Accepted: 20 July 2022 / Published: 21 July 2022
(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)
SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung tissues to investigate the local-mucosal susceptibility and innate immune response to Omicron compared to Delta and earlier SARS-CoV-2 variants of concern (VOC). We show that the replication of Omicron in lung tissues is highly restricted compared to other VOC, whereas it remains relatively unchanged in nasal tissues. Mechanistically, Omicron induced a much stronger antiviral interferon response in infected tissues compared to Delta and earlier VOC-a difference, which was most striking in the lung tissues, where the innate immune response to all other SARS-CoV-2 VOC was blunted. Notably, blocking the innate immune signaling restored Omicron replication in the lung tissues. Our data provide new insights to the reduced lung involvement and clinical severity of Omicron. View Full-Text
Keywords: Omicron; organ culture; interferon response; nasal organ culture; lung organ culture; COVID-19; SARS-CoV-2 Omicron; organ culture; interferon response; nasal organ culture; lung organ culture; COVID-19; SARS-CoV-2
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MDPI and ACS Style

Alfi, O.; Hamdan, M.; Wald, O.; Yakirevitch, A.; Wandel, O.; Oiknine-Djian, E.; Gvili, B.; Knoller, H.; Rozendorn, N.; Golan Berman, H.; Adar, S.; Vorontsov, O.; Mandelboim, M.; Zakay-Rones, Z.; Oberbaum, M.; Panet, A.; Wolf, D.G. SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues. Viruses 2022, 14, 1583. https://doi.org/10.3390/v14071583

AMA Style

Alfi O, Hamdan M, Wald O, Yakirevitch A, Wandel O, Oiknine-Djian E, Gvili B, Knoller H, Rozendorn N, Golan Berman H, Adar S, Vorontsov O, Mandelboim M, Zakay-Rones Z, Oberbaum M, Panet A, Wolf DG. SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues. Viruses. 2022; 14(7):1583. https://doi.org/10.3390/v14071583

Chicago/Turabian Style

Alfi, Or, Marah Hamdan, Ori Wald, Arkadi Yakirevitch, Ori Wandel, Esther Oiknine-Djian, Ben Gvili, Hadas Knoller, Noa Rozendorn, Hadar Golan Berman, Sheera Adar, Olesya Vorontsov, Michal Mandelboim, Zichria Zakay-Rones, Menachem Oberbaum, Amos Panet, and Dana G. Wolf. 2022. "SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues" Viruses 14, no. 7: 1583. https://doi.org/10.3390/v14071583

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